The primary objective of this proposal is to conduct comparative outcome investigation of a highly promising treatment derived from the Cognitive Model of Panic (CMP) vs. applied Relaxation Training in the treatment of Panic Disorder with Agoraphobia (PDA). A comprehensive assessment battery will be administered at pre, mid, posttreatment and at 3, 6, 12, and 24-month follow-ups to monitor the treatments' efficacy, clinical significance and generalization. The mediating influence of stressful life events and individual differences will be examined. Longitudinal monitoring will delineate cognitive, behaviotal, physiological, and psychological adjustment, relapse and the emergence of any psychiatric disorders. Forty-eight patients, meeting DSM-III-R criteria for PDA, will be randomly assigned to the treatments. Protocol therapists, whose treatment integrity will be objectively monitored, will be counterbalanced across treatments. The role of self-directed exposure practice, marital adjustment, response profiles, concordance- disconcordance, need for interim treatment and booster sessions will be compared across conditions. Moreover, the clinical impact of the treatments will be examined by comparing treated patients to normative, non-phobic cohorts as well as using formal clinical significance testing. The proposed study will address critical conceptual, methodological and clinical-research issues regarding their short and long-term efficacy for this chronic and severe anxiety disorder, estimated to afflict 5-11 million Americans. Lyl+B cells are a unique subpopulation of critical importance in the development of autoimmunity, immunodeficiency and B cell malignancy. The goal of this grant is to investigate the immunoregulatory role of hyperdiploid Ly1+B cells obtained from the spleens of NZB mice. Immunoregulation will be investigated in cell transfer experiments in which hyperdiploid splenic Lyl+B cells will be transfused into unirradiated autoimmune and non-autoimmune recipients. Chromosome markers show that the only long-lived donor cells found in these recipients are hyperdiploid LYI+B cells. The effect of in vivo transferred LYI+B cells recipient antibody production both spontaneously produced autoantibody and antibody to exogenous antigens,and recipient B cells subpopulations will be assessed. Hyperdiploid Ly1+B cell hybridomas as well as purified Ly1+B cell will be studied for antibody specificity and VH gene family usage. These results will be compared with conventional peritoneal diploid Ly1+B cell V gene usage. Experiments will determine if diploid Ly1+B cells in young NZB mice develop into hyperdiploid Ly1+B cells genetically programmed fashion or in response to environmental stimuli. The splenic hyperdiploid Lyl+B cells offer a unique opportunity to study the development and function of a singular population of spontaneous occurring B cells. These cells can be used to investigate the role of Ly1+b cells in vivo by virtue of their selective growth advantage and abnormal chromosome markers which allow independent identification in human immune disorders such as rheumatoid artheitis, Leul+ B cells (human analog of Lyl+ B cells) are elevated. In addition, the malignant cell in many chronic lymohocytic leukemias has been identified as a Leu1+ B cell. Becaus this unique subulation of B cells is important in patients with autoimmunit and malignancy, the proposed studies of the role of the murine analog, Lyl- B cells, in immune regulation have important clinical relevance. An uhderitanding of the mechanism of immunoregulation by Lyl+B cells may lead to novel therapeutic intervention in disease.